Osman Nisreen A A, Khalil Alzahraa Ibrahim, Yousef Rehab Kamal
Department of Pathology, Faculty of Medicine, Minia University, Egypt.
Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2961-2970. doi: 10.31557/APJCP.2020.21.10.2961.
This study aimed to investigate the expression of SOX2, SOX9, p53, and β-catenin in hepatocellular carcinoma (HCC) and their correlation with clinicopathological parameters of prognostic importance.
Seventy-five patients were enrolled in this study. All patients had full clinical and follow-up data and available paraffin blocks. Immunohistochemical analysis was performed and correlated with clinicopathological factors and patient survival.
We detected the positive expression of SOX2, SOX9, p53, and β-catenin in 76%, 50.7%, 50.7%, and 77.9% of HCC specimens respectively. All studied markers showed a significant increase in the expression in tumor tissue specimens compared to non-tumor tissue. Both SOX2 and SOX9 expressions were significantly associated with adverse prognostic factors in HCC. Significant positive correlations were found between SOX2 and SOX9 and both p53 and β-catenin expression (r= 0.528, 0.485 and; r = 0.253, 0.327, respectively; p < 0.0001 for both of them). Regarding survival, we found that HCC patients with positive SOX2 and SOX9 expressions had significantly shorter overall survival (p=0.0001, each). Additionally, larger tumor size, tumor grade, high stage, tumor multiplicity, presence of cirrhosis, tumor necrosis, high p53 expression, and positive β-catenin expression were independent predictors of worse survival. A multivariate Cox analysis revealed that tumor grade, stage, p53, and SOX2 expression were independent predictors of unfavorable prognosis in overall survival (p=0.0001, p=0.0001,p=0.033; and p=0.003, respectively).
Our findings might provide an insight into SOX2 and SOX9's role in HCC and suggest that SOX2 might be targeted for HCC therapy.
本研究旨在探讨SOX2、SOX9、p53和β-连环蛋白在肝细胞癌（HCC）中的表达及其与具有预后重要性的临床病理参数的相关性。
本研究纳入75例患者。所有患者均有完整的临床和随访数据以及可用的石蜡块。进行免疫组织化学分析，并将其与临床病理因素和患者生存率相关联。
我们分别在76%、50.7%、50.7%和77.9%的HCC标本中检测到SOX2、SOX9、p53和β-连环蛋白的阳性表达。与非肿瘤组织相比，所有研究的标志物在肿瘤组织标本中的表达均显著增加。SOX2和SOX9的表达均与HCC的不良预后因素显著相关。SOX2和SOX9与p53和β-连环蛋白表达之间均存在显著正相关（r分别为0.528、0.485和0.253、0.327；两者p均<0.0001）。关于生存率，我们发现SOX2和SOX9表达阳性的HCC患者的总生存期显著缩短（两者p均=0.0001）。此外，肿瘤较大、肿瘤分级高、分期高、肿瘤多发、存在肝硬化、肿瘤坏死、p53高表达和β-连环蛋白阳性表达是生存较差的独立预测因素。多因素Cox分析显示，肿瘤分级、分期、p53和SOX2表达是总生存期不良预后的独立预测因素（p分别为0.0001、0.0001、0.033和0.003）。
我们的研究结果可能有助于深入了解SOX2和SOX9在HCC中的作用，并表明SOX2可能成为HCC治疗的靶点。
